This invention relates to novel peptide hydoxamic acid derivatives having useful collagenase inhibitory activity and capable of forming affinity resins for the purification of vertebrate collagenase.
Collagenase is a highly specific, neutral protease which cleaves undenatured collagen at a point about three quarters the distance from the amino terminal end. The enzyme plays a critical role in a variety of normal and pathological states such as resorption of the post-partum uterus, wound healing, rheumatoid arthritis and tumor invasion. Thus, in arthritic and arthrosic diseases, synovial collagenase plays a prominent role in the degradation of the main macromolecules of cartilage, collagen and proteoglycans, since once the collagen fibers of the cartilage are destroyed, joint destruction is irreversible. Accordingly, a specific collagenase inhibitor would be considered as a potential therapeutic agent for use against cartilage destruction in rheumatic diseases. Methods for purification of vertebrate collagenase are useful for the study of the role of collagenase in these and other such pathological conditions.